The effect of DAFNE education, continuous subcutaneous insulin infusion, or both in a population with type 1 diabetes in Scotland.

AIM: To investigate the effect of DAFNE and continuous subcutaneous insulin infusion in clinical practice. METHODS: Within NHS Lothian, continuous subcutaneous insulin infusion started in 2004 and DAFNE education began in 2006. We extracted anonymized data from the national database for all those aged > 18 years with type 1 diabetes having a Dose Adjustment For Normal Eating course or continuous subcutaneous insulin infusion start date (n = 4617). RESULTS: In total, 956 persons received DAFNE education, and 505 had received an insulin pump, 208 of whom had DAFNE education followed by insulin pump. Mean (SD) HbA1c before DAFNE education was 68 (15) mmol/mol (8.4% [1.4%]) and 66 (13) mmol/mol (8.2% [1.2%]) before continuous subcutaneous insulin infusion. In the year following DAFNE education, the mean fall in within-person HbA1c was 3.8 mmol/mol (95% CI 4.0 to 3.4; 0.3% [0.4% to 0.3%]). Those with the poorest control (HbA1c ≥ 85 mmol/mol [9.9%]) experienced the largest decline (15.7 mmol/mol [1.4%]). Those in the lowest HbA1c band at initiation (< 53 mmol/mmol [7.0%]) experienced a rise. In the year following continuous subcutaneous insulin infusion initiation there was a mean fall in within-person HbA1c of 6.6 mmol/mol (6.8 to 6.4; 0.6% [0.6% to 0.6%]). In those with the poorest control (HbA1c ≥ 85 mmol/mol [9.9%]), the mean fall in HbA1c was 22.2 mmol/mol (23 to 21; 2.0% [2.1% to 1.9%]). Continuous subcutaneous insulin infusion effectiveness was not different with or without DAFNE education. The effects of both interventions were sustained over 5 years. CONCLUSIONS: Both DAFNE education and insulin pump therapy had the greatest effect on HbA1c in those with higher baseline values. There was little difference to attained HbA1c when Dose Adjustment For Normal Eating education was introduced before insulin pump therapy.

Iron overload syndrome in the black rhinoceros (Diceros bicornis): microscopical lesions and comparison with other rhinoceros species.

The African black rhinoceros (Diceros bicornis) has adapted to a low iron diet during evolution and is thus prone to iron overload in captivity, which is associated with a number of serious disorders. A S88T polymorphism in the HFE gene has been suggested as a potential genetic basis of increased iron uptake in the black rhinoceros, while the Indian rhinoceros is thought to be unaffected by iron overload in captivity. In the present study, the histopathology and distribution of iron accumulations in five black rhinoceroses with iron overload syndrome were characterized and compared with three Indian rhinoceroses (Rhinoceros unicornis) and one African white rhinoceros (Ceratotherium simum). At necropsy examination, iron storage in black rhinoceroses was not associated with gross lesions. Microscopically, the most consistent and highest degree of iron load was found in the spleen, liver, small intestine and lung. There was minimal fibrosis and single cell necrosis in the liver. Endocrine organs, lymph nodes, heart and kidney were less often and less markedly affected. Unexpectedly, Indian rhinoceroses also showed iron load in the spleen and smaller amounts in organs similar to the black rhinoceros except for in the heart, while the white rhinoceros had only minor detectable iron storage in intestine, liver and lung. Sequence analysis confirmed the HFE S88T polymorphism in black but not in Indian rhinoceroses. The results indicate that Indian rhinoceroses may also be affected by iron storage in captivity, although in a milder form than the black rhinoceros, and therefore challenge the relevance of the S88T polymorphism in the HFE gene of black rhinoceroses as the underlying cause for iron overload.

Metastatic endocervical adenocarcinoma in a western lowland gorilla (Gorilla g. gorilla): no evidence of virus-induced carcinogenesis.

BACKGROUND: Cervical Cancer is the second most common cancer among women. Nevertheless, similar tumours have only been rarely described in Great Apes. This report characterizes the pathological and molecular features of a metastatic endocervical adenocarcinoma in a Western lowland gorilla (Gorilla g. gorilla). METHODS: Necropsy and histopathology was performed to identify the cause of the disease in an cachectic 50-year-old western lowland gorilla. Immunohistochemistry for Ki67, oestrogen receptor alpha and ERBB2 was performed to characterize the tumor. In addition, Pan-herpesvirus and Pan-papillomavirus PCR were used to identify a possible viral cause. RESULTS: The endoccervical carcinoma showed a severe metastatic spread to the lung, brain and bone and was herpesvirus and papillomavirus-negative. Most tumor cells were ERBB2-positive, 15% of tumor cells were Ki67-positive and only few tumor cells had oestrogen receptor alpha expression. CONCLUSIONS: Histopathologically and immunohistochemically, the tumour had striking similarities to human endocervicial adenocarcinomas of the common type. However, PCR analysis failed to identify herpes- or papillomaviral DNA in the tumor at the time of necropsy, thus leaving the question for cause of the disease open.

Oronasal fistula in a 53-year-old hippopotamus (Hippopotamus amphibius).

An oronasal fistula is described in a 53-year-old captive hippopotamus, the animal having shown a nasal discharge, consisting mainly of food particles, during and after feeding for at least 15 years. Necropsy of the emaciated animal revealed an oronasal fistula, measuring 4.5 x 3.5 cm, adjacent to the third left molar tooth, the first and second molars being missing. The fistula was thought to have been caused by an earlier necrotizing alveolitis and osteitis. There was no evidence of rhinitis or aspiration pneumonia. Unrelated findings consisted of a follicular thyroid adenoma and generalized muscle atrophy.

Headspace solid-phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS) for the determination of 5alpha-androst-2-en-17-one and -17beta-ol in the female Asian elephant: application for reproductive monitoring and prediction of parturition.

Asian elephants are not self-sustaining in captivity. The main reasons for this phenomenon are a low birth rate, an aging population, and poor calf-rearing. Therefore, it is essential that reproductive rates had to be improved and there is need for rapid quantitative measures to monitor reproductive functions focussing on estrous detection and the prediction of the period of parturition. The objective of this study was to develop a method which combines headspace solid-phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS) for analyses of 5alpha-androst-2-en-17beta-ol and -17-one to prognose estrous and to predict the period of parturition. SPME was carried out with a CTC Combi Pal system. The course of the luteal phase-specific substance 5alpha-androst-2-en-17beta-ol and -17-one followed a cyclic pattern in which the follicular and luteal phases could be clearly distinguished (mean estrous cycle length, 15+/-1.4 weeks). Based on daily urine samples, estrous prognosis might be possibly based on the initial 5alpha-androst-2-en-17beta-o1 increase at the end of the follicular phase. Parturition prognosis was performed in three elephant cows based on the 5alpha-androst-2-en-17beta-o1 drop to baseline levels 5-4 days prior parturition. Experiments revealed that 5alpha-androst-3alpha-ol-17-one and probably 5alpha-androst-3alpha-ol-17beta-ol are generated from sulfate conjugates by a thermal process.

Severe veno-occlusive disease after allogeneic bone marrow or peripheral stem cell transplantation--role of transjugular intrahepatic portosystemic shunt (TIPS).

AIMS: Veno-occlusive disease of the liver is a severe complication of allogeneic bone marrow or peripheral stem cell transplantation with a high mortality. In its severe form, the portal vein is used as an outflow tract for the arterial hepatic perfusion. A portosystemic side-to-side shunt, e.g. a transjugular intrahepatic portosystemic shunt, may facilitate portal outflow thus increasing hepatic (i.e. arterial) perfusion. METHODS: The effect of a transjugular shunt on liver function and blood flow was studied in three patients receiving shunt treatment 0-2 days after the diagnosis of severe veno-occlusive disease occurring 28, 20, and 17 days after allogeneic transplantation for acute myeloid leukemia, Hodgkin's disease and chronic myeloid leukemia, respectively. RESULTS: The transjugular shunt reduced the portosystemic pressure gradient from 23 to 8, 18 to 5, and 33 to 13 mmHg in patients 1, 2, and 3, respectively, increased the stagnant portal vein flow to normal, and decreased the arterial resistive index, indicating an increase in the arterial perfusion of the liver. This was accompanied by rapid relief from abdominal pain and removal of ascites. The AST concentration dropped from 1230, 417, and 2930 U/l before to 93, 20, and 41 U/l and the PT-time ratio improved 3-7 days after shunt treatment while the bilirubin concentration continued to rise until the patients died 26, 42, and 33 days after transplantation from multiorgan failure (two patients) or intracerebral hemorrhage. CONCLUSIONS: The transjugular shunt may have improved abdominal and hepatic perfusion and prevented further necrosis of hepatocytes. It did not, however, affect jaundice or survival, which was limited by extrahepatic complications.

Genetic and ultrastructural characterization of a European isolate of the fatal endotheliotropic elephant herpesvirus.

A male Asian elephant (Elephas maximus) died at the Berlin zoological gardens in August 1998 of systemic infection with the novel endotheliotropic elephant herpesvirus (ElHV-1). This virus causes a fatal haemorrhagic disease in Asian elephants, the so-called endothelial inclusion body disease, as reported from North American zoological gardens. In the present work, ElHV-1 was visualized ultrastructurally in affected organ material. Furthermore, a gene block comprising the complete glycoprotein B (gB) and DNA polymerase (DPOL) genes as well as two partial genes was amplified by PCR-based genome walking and sequenced. The gene content and arrangement were similar to those of members of the Betaherpesvirinae. However, phylogenetic analysis with gB and DPOL consistently revealed a very distant relationship to the betaherpesviruses. Therefore, ElHV-1 may be a member of a new genus or even a new herpesvirus subfamily. The sequence information generated was used to set up a nested-PCR assay for diagnosis of suspected cases of endothelial inclusion body disease. Furthermore, it will aid in the development of antibody-based detection methods and of vaccination strategies against this fatal herpesvirus infection in the endangered Asian elephant.

[Pancreatic and biliary tract tumors--diagnosis: ultrasonic diagnosis--endosonography]. / Pankreas- und Gallenwegstumoren--Diagnostik: Ultraschall--Endosonographie.

Pancreaticobiliary tumors are mostly adenocarcinomas with a poor 5-year survival of less than 2%. Early diagnosis of resectable tumors improves outcome. Conventional ultrasound (US) is non-invasive and is the first modality employed on suspicion of these tumors. With adequate skills and equipment, pancreatic tumors from 1.5 cm in diameter can be detected. By contrast, US is less sensitive in the detection of lymph node involvement and infiltration of blood vessels. Depending on the location tumors of the biliary tract appear as a mass lesion intrahepatically or within the gallbladder. Perihilar and extrahepatic bile duct carcinomas cause proximal duct dilatation which is readily detected by US. Again, sensitivity in the detection of lymph node metastases or portal vein invasion is limited. Endoscopic ultrasound (EUS) has emerged as the method of choice in detecting small pancreatic tumors (e.g. < 2 cm in diameter). An accuracy of over 90% in T-staging and blood vessel infiltration can be achieved whereas lymph node metastases are correctly diagnosed in only 67% of cases. EUS-guided biopsy is readily performed using a curved array scanner. This technique enables neurolysis of the coeliac plexus in patients with heavy pain. EUS adds valuable information in cases of distal extrahepatic bile duct cancer. The role of EUS is limited in perihilar and intrahepatic cholangiocarcinoma. Staging and palliative therapy of perihilar carcinoma is still a domain of endoscopic retrograde cholangiography. Intraductal EUS is restricted to specialized centers and plays no role for routine purposes.

[Value of manometry]. / Stellenwert der Manometrie.

Manometry of the esophagus is essential in the diagnostic workup of patients with motility disorders of the esophagus. Before manometry organic diseases causing the symptoms should be excluded by a esophago-gastroscopy and/or a barium swallow meal. Indications for manometry are noncardiac chest pain, dysphagia of unknown origin, primary or secondary motility disorders of the esophagus and preoperative assessment before antireflux surgery.

Vascular endothelial growth factor in the sera and effusions of patients with malignant and nonmalignant disease.

BACKGROUND: Clinical data clearly indicate a correlation between tumor neovascularization, aggressiveness of tumor growth, and metastatic spread. One of the key factors capable of stimulating tumor angiogenesis is vascular endothelial growth factor (VEGF). Using an immunoassay for VEGF, we assessed the levels of soluble VEGF in the sera and effusions of patients with malignant and nonmalignant disease as well as in the sera of healthy controls. METHODS: Using a sandwich enzyme-linked immunoadsorbent assay, the concentration of VEGF was measured in serum specimens (n=445) and effusions (n=56) collected from a total of 212 patients with various types of cancer, 88 patients with nonmalignant disease, and 145 healthy individuals. RESULTS: Low and rather stable levels of VEGF were detected in the serum of healthy individuals (median, 294 pg/mL; range, 30-1752 pg/mL; 95th percentile, 883 pg/mL). Compared with healthy individuals, serum levels in patients with acute infections were elevated (P=0.03), whereas patients with chronic cirrhosis had lower serum VEGF levels. Among patients with various types of neoplasia, VEGF serum levels in patients with ovarian or gastrointestinal carcinoma were significantly higher than in healthy individuals. Moreover, VEGF concentrations in sera from patients with metastatic disease were higher than in sera from patients with localized tumors. Maximum serum concentrations of VEGF (median, 1022 pg/mL; range, 349-7821 pg/mL) were found in patients with metastatic ovarian carcinoma. Median VEGF levels (and ranges) in malignant effusions were up to 10-fold higher than in matched serum samples: 5528 pg/mL (468-49269 pg/mL) in ovarian carcinoma, 885 pg/mL (77-14,337 pg/mL) in breast carcinoma, and 813 pg/mL (372-18,331 pg/mL) in gastrointestinal carcinoma. In contrast, ascitic fluid from patients with cirrhosis contained only 303 pg/mL (median, range 116-676 pg/mL) of VEGF, corresponding to the low serum levels in this patient group. CONCLUSIONS: Depending on the tumor type, elevated levels of VEGF are detectable in the serum of only 0-20% of patients with localized cancer but in 11-65% of patients with metastatic cancer. Of cytology-proven malignant ascites or peritoneal exudates from various malignancies, 46-96% show VEGF levels above the upper limit (95th percentile, 676 pg/mL) of nonmalignant ascites. Maximum VEGF concentrations in malignant effusions indicate abundant local release of VEGF within the pleural or peritoneal cavity. These results suggest that VEGF might play an important role in tumor progression and the formation of malignant effusions. Further studies are warranted to determine the clinical value of soluble VEGF as a tumor marker, a prognostic factor, and a surrogate indicator of tumor angiogenesis.

Platelet aggregation and platelet-derived growth factor inhibition for prevention of insufficiency of the transjugular intrahepatic portosystemic shunt: a randomized study comparing trapidil plus ticlopidine with heparin treatment.

Intimal proliferation at the interface between prosthetic material and tissue is an intrinsic phenomenon of stenting and the major cause of insufficiency of the transjugular intrahepatic portosystemic shunt (TIPS). For its prevention, a randomized study was performed comparing standard heparin treatment with a combination of trapidil, a drug with anti-platelet-derived growth factor (PDGF) activity, and ticlopidine, a platelet aggregation inhibitor. Ninety patients with cirrhosis who received a transjugular shunt were randomized, and 84 patients completed the trial. Group 1 (n = 42) received a bolus of heparin (12 to 24 U/kg) at shunt placement, followed by 1 week of intravenous and 4 weeks of subcutaneous heparin treatment. Group 2 (n = 42) received the same heparin bolus, followed by a 1-day intravenous heparin treatment and a 6-month treatment with trapidil (400 mg/d) and ticlopidine (250 mg/d). Shunt function was assessed by duplex-sonography and angiography. Stenoses were classified according to their location as type 1 (within the stent) and type 2 (in the draining hepatic vein). The estimated rate of overall stenoses (intention-to-treat analysis) at 1 year showed a significant reduction in patients receiving trapidil and ticlopidine (group 2) as compared with heparin (33 vs. 57%; P =.047). There was no difference in the estimated 1-year rate of type 1 stenoses between the two groups, but there was a significant reduction in type 2 stenoses (group 1: 58%, group 2: 19%; P =.016). The treatment effect continued after withdrawal of the drugs and was accompanied by a decreased incidence of rebleeding. The study demonstrates that the incidence of type 2 stenosis of the transjugular shunt can be reduced by combined inhibition of platelet aggregation and PDGF activity. The findings may be of relevance not only for the transjugular shunt, but also for other stent applications, e.g., vascular and biliary, as well as for bypass and shunt surgery.

[Sex steroid profiles and ovarian activities of the female panda Yan Yan in the Berlin Zoo]. / Sexualsteroidprofile und Ovaraktivitäten des Pandaweibchens YAN YAN im Berliner Zoo.

The nine years old giant panda YAN YAN was received in April 1995 on loan for 5 years to the Berlin Zoo. Urine samples were collected daily or every second day from April 1995 to June 1996 in order to follow up sex hormone secretions and ovarian activities. Conjugated steroids were hydrolysed, extracted and measured with two enzyme immuno assays (EIA) being specific for either total oestrogenes or pregnandiol. The evaluation of the hormone secretion pattern yielded the following results: There is a significant synchronous cross correlation between estrogen and progestin metabolites secretion indicating its simultaneous synthesis. In addition, we found a regular increase and decrease of both hormones with a 13 days interval. This secretory pattern indicates repeating development and atresia of follicle cohorts with a cycle length of about 13 days. Only a single period of slightly elevated oestrogen synthesis was monitored in Feb. 96 without any signs of oestrus. Obviously the stimulation of ovarian function was insufficient for complete ovulation and corpus luteum formation.

The transjugular stent implantation for the treatment of malignant portal and hepatic vein obstruction in cancer patients.

BACKGROUND: The increase in portal vascular resistance is a significant complication of metastatic disease to the liver or locally advanced cancer, e.g., biliary cancer. PATIENTS AND METHODS: This paper describes the successful palliative treatment of two cancer patients with portal hypertension presenting with the symptoms of tense ascites, mesenteric congestion, and severe variceal bleeding. By creating a stenttract between a hepatic vein and a main branch of the portal vein and/or by placing an extendable stent into the portal vein, the transjugular intrahepatic portosystemic stent-shunt (TIPS) technique was used to decompress the portovascular system. RESULTS: The TIPS-technique offers a new, safe and effective palliation for malignant portal hypertension. In both patients, the symptoms of the portal hypertension disappeared after the procedure. This was accompanied by a significant improvement of the patients performance status allowing an early ambulation. CONCLUSION: Our findings demonstrate the feasibility and effectiveness of the TIPS procedure as a minimal invasive treatment for portal vein decompression in selected tumor patients.

[Current ascites therapy]. / Aktuelle Aszitestherapie.

Ultrasonography detects ascites easily even in trace amounts. 80% of the cases are caused by hepatic disease, in the remaining 20% cancer, inflammation, pancreatic, renal, or cardiac disease can be found. The underlying disease should be investigated by few inexpensive laboratory test from serum, urine and ascites and by abdominal sonography. Hepatic ascites is caused by portal hypertension and disturbances of humoral factors. Sodium retention, peripheral, vasodilation, hyperdynamic circulation and progressive renal vasoconstriction lead to a stepwise deterioration of patients condition. Treatment with diuretics (furosemide, torsemide, or xipamide and spironolactone) and sodium-restriction (< 60 mval per day) control 85-90% of the cases with hepatic ascites. If this regimen fails, non-compliance, spontaneous bacterial peritonitis, hyponatremia or additional complications such as renal failure, Budd-Chiari syndrome or tumor should be considered. Ten to 15% of the patients develop refractory ascites and finally hepatorenal syndrome and have a poor prognosis. Early liver transplantation should be considered. Large volume paracentesis with albumin substitution is a therapeutic option in these patients. The transjugular intrahepatic portosystemic stent-shunt (TIPS) may be superior for patients with concurrent esophageal varices or hepatorenal syndrome. If TIPS is considered the patient should be referred to an experienced center. The peritoneo-venous shunt is restricted to rare indications. In the future, new drugs such as antagonists of endothelins or of the antidiuretic hormone may offer new therapeutic options.

The transjugular intrahepatic portosystemic stent-shunt procedure for refractory ascites.

BACKGROUND: Previous studies have suggested that the transjugular placement of an intrahepatic stent to establish a portosystemic shunt is an effective treatment of uncomplicated ascites accompanying variceal bleeding. We studied the stent shunt for use in patients with liver cirrhosis and ascites refractory to medical treatment. METHODS: Fifty of 62 consecutive patients with cirrhosis and refractory ascites (18 with Child-Pugh class B liver disease and 32 with class C) were treated with the stent shunt--an expandable stent of metallic mesh placed between a major branch of the portal vein and one of the hepatic veins. Patients were followed for a mean (+/- SD) of 426 +/- 333 days. Those with advanced cancer, severe heart failure, or severe liver failure were excluded. RESULTS: The stent shunt was successfully placed in all patients and reduced the pressure gradient between the portal vein and the inferior vena cava by an average of 63 percent. Thirty-seven patients (74 percent) had complete responses (total remission of ascites within three months), and nine patients (18 percent) had partial responses (ascites detected by ultrasound but with no need for paracentesis). Four patients did not respond, including two who died within two weeks of shunt placement. After the procedure, 25 patients had hepatic encephalopathy, as compared with 20 patients before the procedure; although encephalopathy improved in 3 patients, new encephalopathy developed in 8 patients. In the 28 of the 33 patients followed for more than six months who were evaluated, the mean serum creatinine concentration was 1.5 +/- 0.09 mg per deciliter (133 +/- 8 mumol per liter) before placement of the stent shunt, 1.5 +/- 1.6 mg per deciliter (133 +/- 141 mumol per liter) one week after the procedure, and 0.9 +/- 0.3 mg per deciliter (80 +/- 27 mumol per liter) after six months (P = 0.008 for the comparison of concentrations before and six months after the procedure). Renal function did not improve in the six patients with organic kidney disease. Procedure-related complications developed in 16 patients, including intraabdominal bleeding requiring blood transfusions in 2 patients. Thrombotic occlusion of the stent shunt occurred within two weeks in 5 patients, and later insufficiency of the shunt occurred in 16 patients, including 12 with recurrence of ascites after complete remission. During followup, an additional 29 patients died--10 of progressive liver disease and 19 of other causes. Survival for at least one year was associated with a patient's being under 60 years of age, having a serum bilirubin level before placement of the stent shunt of less than 1.3 mg per deciliter (22 mumol per liter), and having a complete response. CONCLUSIONS: Our findings in an uncontrolled prospective study suggest that the transjugular intrahepatic porto-systemic stent-shunt procedure was an effective treatment for many patients with liver cirrhosis and refractory ascites, but mortality from underlying diseases was substantial.

Clinical relevance of abnormal liver findings with ultrasound.

In this study we compared the ultrasound findings of 203 hospitalized patients with a variety of reference methods: biopsy, computed tomography and laboratory liver function tests with the aim of defining their clinical relevance. The ultrasound findings were assignable to 3 groups: normal, descriptive and definitive. When ultrasound described a liver as normal, or showing "increased echogenicity" or "altered configuration", the figures of normal clinical reference methods were almost identical (i.e., 70% normal). When a definitive ultrasound diagnosis ("cirrhosis", "fatty liver" or "cardiac congestion") was made, the percentage of otherwise normal livers decreased to less than 20% and was 0% for cirrhosis and cardiac congestion. The positive predictive value for a single abnormal criterion in ultrasound was between 16% and 21%, while for a definitive diagnosis it was between 67% and 100%. Many of our patients, however, had additional risk factors for liver abnormalities, such as obesity, diabetes mellitus or chemotherapy for malignancies. These risk factors can induce morphological parenchymal alterations without blood test abnormalities and, although correctly diagnosed by ultrasound, elude other reference methods in patients without biopsy. In conclusion, the finding of a single abnormal criterion of liver abnormality in ultrasound should be treated with caution. Ultrasound diagnoses of "fatty liver", "cirrhosis", diagnosed by additional signs of portal hypertension, or "cardiac congestion", yield more information. A normal ultrasound does not exclude the presence of fatty liver or cirrhosis.

[Current status of abdominal pancreatic ultrasound. A retrospective analysis of 585 pancreatic ultrasound examinations]. / Aktueller Stellenwert der abdominellen Pankreassonographie. Eine retrospektive Analyse von 585 sonographischen Pankreasuntersuchungen.

BACKGROUND: In the recent years several investigations focused on the diagnostic value of abdominal ultrasonography in pancreatic disorders. However, the diagnostic accuracy in these studies ranged between 40 and 90% probably related to variations in study design and other methodologic criteria. PATIENTS: We examined retrospectively 585 patients subdivided into six subgroups. 385 patients had a clinical question aimed at the pancreas and the remaining 200 functioned as screening patients. RESULTS: Using laboratory tests, CT, ERCP, surgery and autopsy as reference methods the positive predictive value for all pancreatic disorders was 85% with the best results for chronic pancreatitis (86% versus 77.5% for acute pancreatitis and 79.5% for malignant tumors). The prevalence of pancreatic disease in symptomatic patients was 28.6% versus only 2.5% in the screening groups. Therefore no significant differences could be detected in groups where the pancreas was not clearly visualized and groups with negative sonographic findings (4% false negative findings versus 1%, respectively). In groups with suspected pancreatic disease the negative predictive value was 86% which was independent of the visualization of the pancreas. CONCLUSION: In summary positive sonographic findings have a high predictive value for pancreatic disorders and negative results are not more reliable than missing visualization of the pancreas. The positive predictive value is independent from the kind of pancreatic disease and in screening examinations negative findings and findings without clearly visualization of the pancreas have both high negative predictive values.

Hepatic progenitor populations in embryonic, neonatal, and adult liver.

Oval cells, small cells with oval-shaped nuclei, are induced to proliferate in the livers of animals treated with carcinogens and are thought to be related to liver stem cells and/or committed liver progenitor cell populations. We have developed protocols for identifying and isolating antigenically related cell populations present in normal tissues using monoclonal antibodies to oval cell antigens and fluorescence-activated cell sorting. We have isolated oval cell-antigen-positive (OCAP) cells from embryonic, neonatal, and adult rat livers and have identified culture conditions permitting their growth in culture. The requirements for growth of the OCAP cells included substrata of type IV collagen mixed with laminin, basal medium with complex lipids and low calcium, specific growth factors (most potently, insulin-like growth factor II and granulocyte-macrophage colony-stimulating factor), and co-cultures of embryonic, liver-specific stroma, strongly suggesting paracrine signaling between hepatic and hemopoietic precursor cells. The growing OCAP cultures proved to be uniformly expressing oval cell markers but were nevertheless a mixture of hepatic and hemopoietic precursor cells. To separate the hepatic and hemopoietic subpopulations of OCAP cells, we surveyed known antibodies and found ones that uniquely identify either hepatic or hemopoietic cells. Several of these antibodies were used in panning procedures and fluorescence-activated cell sorting to eliminate contaminant cell populations, particularly hemopoietic and endothelial cells. Using specific flow cytometric parameters, three cellular subpopulations could be isolated separately that were identified by immunochemistry and molecular hybridization assays as probable: (i) committed progenitors to hepatocytes; (ii) committed progenitors to bile ducts; or (iii) a mixed population of hemopoietic cells that contained a small percentage of hepatic blasts that are possibly pluripotent. The hepatic precursor cells have been characterized using immunochemistry, flow cytometry, and molecular hybridization assays. The hepatic blasts are small (7-10 microns) cells with high nuclear to cytoplasmic ratios and with minimal complexity of the cytoplasm. Cultures of the committed progenitors were found to differentiate into cells with recognizable parenchymal cell fates. We discuss our studies in the context of our model of the liver as stem cell and lineage system and suggest that a slow, unidirectional, terminal differentiation process, paralleling more rapid ones in the skin or gut, occurs at all times in the liver and is thought to vary primarily in kinetics during quiescent versus regenerative states.(ABSTRACT TRUNCATED AT 400 WORDS)